Topical and oral delivery of arginine to cause beneficial effects

ABSTRACT

The use of orally administered L-arginine in conjunction with a topical preparation for producing enhanced blood flow in tissue thus causing beneficial effects such as warming cold tissue of the hands and feet, promoting hair growth on bald scalp tissue, promoting healing of superficial ulcers such as leg ulcers in persons with diabetes, and overcoming male erectile failure (impotence) is disclosed. Specifically, use of orally administered L-arginine in conjunction with this is topical preparation provides local delivery of the amino acid L-arginine, an important biological precursor to the main substance which is responsible for relaxation of blood vessels permitting enhancement of blood flow. In the preferred embodiments, the L-arginine is provided so that it can be topically applied to the cold tissue. The preparation also contains an agent which aids in the transfer of L-arginine into the tissue. In the preferred embodiments this agent overcomes the resistance to transfer caused by the high charge density of L-arginine. In the preferred embodiments this means is high ionic strength created by addition of sodium chloride. This preparation, when topically applied to cold tissue, warming begins within 10 to 45 minutes and is sustained for periods as long as 2 to 18 hours. Further this preparation when applied nightly to bald scalp tissue for a period of time causes substantial growth of hair on the bald scalp, causes the healing of superficial ulcers such as leg ulcers and overcomes impotence.

BACKGROUND

[0001] 1. Field of the Invention

[0002] This invention relates to the use of L-arginine orally alone orin conjunction with topical application of a cream, gel, or othervehicle which contains substances such as L-arginine which deliversthese substances into tissue for the purpose of producing beneficialeffects such as warming of cold or cool tissues, growth of hair on thescalp, healing of leg ulcers secondary to diabetes or confinement tobed, relief of impotence, as well as beneficial effects throughrestoration of natural mechanisms based on improvement of local bloodsupply.

[0003] 2. Prior Art

[0004] Approaches to improving local blood flow have been many andconsist of both systemic and topical approaches. Many beneficial effectscould be obtained should improvement in local blood flow be achievedsince impairment of local blood flow causes a variety of negativeconsequences. Among these are cold hands and feet, baldness, leg ulcers,certain forms of impotence, as well as a variety of other things.Approaches to warming cold tissue including cold hands, fingers, feetand toes constitute one section of the prior art. Many persons sufferfrom cold hands, feet or other body parts. This is often caused byinsufficient blood flow in the cold tissue. Previously cold hands orfeet have been treated by wearing warm socks or gloves, sometimes evensocks or gloves which are mechanically heated. The use of hot packs andglove or shoe inserts which generate heat through chemical reactions hasalso been a potential solution. Certain liniments which are essentiallyirritants, such as those containing the red pepper derived substance,capsicum fall into this category. More recently, topical creamscontaining nitroglycerine have been used. See H. Natsuda et al.,Ryumachi 34, 849 (1994). All of these approaches work at one level oranother though are often extremely transient in nature. Nitroglycerinecreams also have the disadvantage that nitroglycerine is a cardioactivedrug, raising concerns of effects on the heart.

[0005] It has been recognized that deficiencies in blood flow in thescalp occur in male pattern baldness. See G. Duplechain et al., J.Lousiana State Med Soc. 146, 7 (1994); P Klemp et al., J InvestsDermatol 95, 725 (1989); S Toshitani et al., J Dermatol 17, 240 (1990).Topical minoxidil has been used as an agent for hair growth in malepattern baldness with varying results. Though the suggestion has beenmade that minoxidil operates through increase in the blood supply to thescalp, many investigators have failed to show such an effect. See E deBoer et al., Acta Dermato- Venereoligica 68, 271 (1988); C Bunker etal., British J Derm 117, 668 (1987).

[0006] The fundamental fact that cold tissue of the hands, fingers, feetand toes as well as other cold tissue is caused by insufficient bloodflow to the tissue has been suggested. It has further been suggested bysome that the use of increased blood flow through relaxation of bloodvessels, particularly small and very small vessels may be of use inwarming cold tissue. However reasonable this suggestion, many attemptsto demonstrate warming by use of agents which produce vasodilation andtherefore increased blood flow have produced negative results. See NDietz et al., J Appl Physiol 76, 2047 (1994); S Whitmore et al., JRheumatol 22, 50 (1995); S Singh et al., Eur J Clin Invest 25, 182(1995). The only report of modest temporary success involved the use ofnitroglycerine. See H Natsuda et al., Ryumachi 34, 849 (1994). The useof the nitric oxide precursors such as L-arginine to produce warmingsecondary to vasodilation has been suggested. And a variety of indirectand non-definitive experiments have been conducted using oraladministration. See M. Sonntag et al., Pflugers Arch 420,194 (1992); A.Agostoi et al., Int J Clin Lab Res 21, 202 (1991). Thus, while theliterature contains suggestions that vasodilation by administration oforal L-arginine, the precursor of nitric oxide (endothelium-dependentrelaxing factor), no reports exist of success in producing warming oftissue using this agent. In fact Dietz (see N Dietz et al., J ApplPhysiol 76, 2047 (1994)) concludes from his data that “These datasuggest that NO (nitric oxide) does not play a major role in cutaneousvasodilation during body heating in humans.” Further Singh (see S Singhet al., Eur J of Clin Invest 25, 182 (1995)) in a study of patients withRaynaud's phenomenon (severely cold hands and/or feet) concludes thatL-arginine failed to cause vasodilation (and therefore warming) inpatients with Raynaud's phenomenon.

[0007] The literature contains no suggestions or examples of the use ofL-arginine in any mode of administration for the growth of hair in malepattern baldness, healing of ulcers of the skin, impotence or for anyother purpose.

[0008] It has long been recognized that impaired blood flow to the penisis a major cause of erectile failure (impotence) in men. See A Moradianet al. Am J. Med 85, 748, (1988); T Hwang et al. J Formosan Med Assoc89, 992 (1990). Further it has been recognized by using isolated tissuein vitro and in animal experiments that nitric oxide is an importantmediator of relaxation of the vessels in penile cavernous tissue. See HKirkeby et al. Acta Physiol Scand 149, 385 (1993). Topicalnitroglycerine has been used in the treatment of impotence because ofits ability to dilate vessels. The results were inconclusive and thetreatment not well tolerated because of the cardiac response tonitroglycerine. See S Negelev J Urology 143, 586 (1990).

[0009] It was discovered that topical application of the nitric oxideprecursor, L-arginine, in its various forms including orally alone or inconjunction with a variety of topical preparations, either by themselvesor with other agents to aid in penetration such as a high ionic strengthenvironment, neutralization of its charge in a complex or by othermeans, or included in a liposome or other biological carrier, whenadministered to cold or cool tissue causes a substantial and prolongedwarming effect in the tissue, grow hair on bald scalp, facilitatehealing of superficial ulcers such as leg ulcers and overcome impotencein many subjects.

[0010] In accordance with that invention, oral arginine by itself or incombination with a penetrating cream containing L-arginine at aconcentration sufficient to produce an effect and sodium chloride orother salt at a concentration sufficient to create a hostile biophysicalenvironment for the L-arginine in the cream is applied to the cold orcool tissue alone and/or in conjunction with oral arginine, exerts awarming effect which is prolonged, often lasting from 2-18 hours. Inpersons with very cold tissue (for example 22° C.) this warming effectcan have a magnitude of 10° C. or more.

[0011] Further, in accordance with this invention, oral L-arginine aloneor in conjunction with a penetrating cream containing L-arginine in aconcentration sufficient to produce the desired effect along with sodiumchloride or other salts at a concentration sufficient to produce ahostile biophysical environment when applied to bald areas of the scalpnightly either alone and/or in conjunction with oral arginine, producedgrowth of new hair within one month and substantial growth of hairwithin 3-4 months.

[0012] Yet further, in accordance with this invention, oral argininealone or in conjunction with a penetrating cream containing L-argininein a concentration sufficient to produce the desired effect along withsodium chloride or other salts at a concentration sufficient to producea hostile biophysical environment when applied locally as the creamdirectly to the penis either alone and/or in conjunction with oralarginine, was effective in overcoming impotence.

[0013] Consequently, with the discovery of the present invention, ameans to warm cold and cool tissue, a problem shared by many, wasdeveloped for improving this uncomfortable and often painful problem inhuman health has been found. Further with the discovery of the presentinvention, a means to restore hair growth on a bald portion of scalp hasbeen found. Still further, with the discovery of the present invention,a means effect healing of superficial ulcers such as leg ulcers has beenfound. Yet further, with the discovery of the present invention, a meansto overcome impotence in many men has been found.

[0014] These and other objects and features of the present inventionwill become apparent to those skilled in the art from reading thedescription of the invention, which follows.

SUMMARY OF THE INVENTION

[0015] Accordingly, several objects and advantages of the instantinvention are to warm cold tissue in hands, feet or other tissue byincreasing blood flow in the tissue means of enhancement of the body'snatural mechanisms. It is further an object and advantage of the instantinvention to prophylactically prevent tissue from becoming cold by useprior to entering into situations which induce cold hands and feet suchas skiing or other winter outdoors activities. It is further an objectand advantage of the instant invention to induce the growth of hair onbald portions of human scalp by means of enhancement of the body'snatural mechanisms. It is yet another object of the instant invention toinduce healing of superficial ulcers of the limbs by means ofenhancement of the body's natural mechanisms. It is still furtheranother object of the instant invention to provide a means forovercoming impotence in many men.

[0016] In preferred embodiments, the delivery vehicles are capsules ortablets containing L-arginine used alone or in conjunction with apenetrating cream. In the cream the L-arginine is present as L-argininehydrochloride in a concentration sufficient to produce the desiredeffect and the agent which creates the hostile biophysical environmentis sodium chloride at a concentration sufficient to aid in tissueabsorption.

PREFERRED EMBODIMENTS

[0017] The preferred embodiment consists tablets or capsules containing200-500 mg of L-arginine to be used alone or in conjunction with a basecream with the properties of excellent absorption into the skin whichalso contains L-arginine hydrochloride (15% w/v) and sodium chloride(10% w/v). The components of the base cream may be those commonly foundin hand creams. The purpose of L-arginine hydrochloride is to provide aprecursor to the molecule, nitric oxide, NO. The purpose of the sodiumchloride is to provide a high ionic strength environment for the highlycharged molecule, L-arginine. The base cream containing L-arginine andsodium chloride is the agent which is applied to the hands and/or feetto produce to produce a warming effect in the tissue, to produce hairgrowth or to effect healing of ulcers such as leg ulcers, or directly tothe penis in order to aid in overcoming impotence.

[0018] The treatment consisting of oral administration of capsules ortablets containing L-arginine used alone or in conjunction with thecream acts effectively to warm cold tissue such as hands, fingers, feet,toes or other tissue when applied to the tissue and rubbed into thetissue to assure maximal absorption. The warming effect, caused byincreased blood flow in the tissue is not instant but begins within 5 to20 minutes. The effect is long lasting. Often the tissue remains warmfor more than 2 to 18 hours. The treatment consisting of oraladministration of capsules or tablets containing L-arginine used aloneor in conjunction with the cream acts effectively to induce hair growthon bald human scalp when applied nightly to the bald area each night forseveral months. Hair growth is naturally a slow process. However,substantial hair growth is achieved over large areas of scalp withresults becoming evident in a few weeks and substantial within severalmonths. The cream further acts to promote healing of superficial ulcerssuch as those sometimes found on the legs of persons with severediabetes. Application twice daily for a period of two weeks causessubstantial healing and in many cases complete healing is achievedwithin this time period or slightly longer (3-4 weeks). Further thetreatment consisting of oral administration of L-arginine used alone orin conjunction with the cream when carried out daily for a period of7-10 days and then maintained with daily administration causessubstantial relief from impotence in many men.

OTHER EMBODIMENTS

[0019] Other active agents

[0020] While L-arginine hydrochloride is the preferred active agentbecause it is the agent in nature itself, it is non-toxic, is highlysoluble and it is inexpensive, other agents could be used which are alsoprecursors or donors of nitric oxide. These include the salt, arginineglutamate, the salt, arginine butyrate, and esters of arginine such asarginine ethyl ester or arginine butyl ester as well as other donors ofnitric oxide.

[0021] In the case an alternative active agent were used it would besimply substituted for L-arginine in a delivery preparation and thepreparation used as in the case of the L-arginine preparation.

[0022] Other means of effecting absorption

[0023] A variety of means for effecting absorption of the active agentfrom the topical cream might be envisioned. One principle behind theabsorption of a highly charged molecule such as L-arginine into tissueis to either create a biophysically hostile environment in the deliveryvehicle such that L-arginine would prefer to be in tissue, or to packageL-arginine in such a way that it is carried into tissue or neutralizeits charge by derivitization or forming a neutral salt. Examples ofbiophysically hostile environments, include but are not limited to, highionic strength, high or low pH, and highly hydrophobic environments.Examples of packaging which would be carried into tissue includesliposomes or emulsions of collagen, collagen peptides or othercomponents of skin or basement membrane. Examples of neutralization ofcharge include the salt, arginine glutamate which is electronicallyneutral.

[0024] In each case of creating a hostile biophysical environment forthe active agent, the agent was added to an appropriate preparation. Inthe case of creating a high ionic strength ions such as but not limitedto sodium chloride, potassium chloride, choline chloride, lithiumchloride, alone or in combination were added in high concentration.Other highly charged molecules such as polylysine, polyglutamine,polyaspartate or copolymers of such charged amino acids may be used tocreate the hostile biophysical environment. Alternatively a hostilebiophysical environment may be created by placing the highly chargedL-arginine in an hydrophobic, oily environment such as in an oil-basedcream containing little or no water.

EXAMPLE 1

[0025] In this example a person with very cold fingers was provided withthe above warming cream consisting of a delivery vehicle of penetratingcream, L-arginine hydrochloride (15% w/v), and sodium chloride (10%w/v). The surface temperature of the subject fingers of the left handvaried from 21 to 24° C. The warming cream was applied through rubbinginto the skin. Surface temperatures of each finger were measured each 15minutes for the initial hour. At 15 minutes following administration ofthe warming cream the effect had begun to occur with surfacetemperatures or various fingers rising to 26 to 29° C. The maximaleffect was reached by 45 minutes with surface temperatures of variousfingers becoming 31 to 34° C. The effect was sustained at least 4 hours.

EXAMPLE 2

[0026] In this example a 53 year old man with baldness consisting of aseverely receding hairline as well as large “bald spot” on the top rearof his head was provided with a penetrating cream containing L-argininehydrochloride (15% w/v) and sodium chloride (10% w/v). The cream wasapplied to the bald areas each night before going to bed and was rubbedin extensively for maximal absorption. New hair growth was noted within2-3 weeks. Within 4 months the receding hairline (previously 4 cm ofbald skin) had returned to normal and the “bald spot” previously morethan 7 cm in diameter had been reduced to an area of less than 2 cm witheven this area showing some new hair growth.

EXAMPLE 3

[0027] In a 54 year old man with a history of impotence administrationof 1.5 g L-arginine daily in the form of oral capsules combined withtwice daily administration of a penetrating cream containing L-argininehydrochloride (15% w/v) and sodium chloride (10% w/v) directly to thepenis for 7 days brought initial relief from the symptoms of impotenceand allowed the subject to resume normal sexual activity. This relief ofsymptoms was maintained by continuation of the treatment daily.

[0028] Accordingly, it can be seen that in the present invention I haveprovided a method and agents, which when applied to cold, and oftenpainful tissue, an increase in skin temperature results throughutilization of one of the body's own mechanisms for producing warmth.This effect is achieved by providing the biochemical substrate at thelocal site from which the controlling substance, nitric oxide, isproduced. Nitric oxide causes increases in local blood flow whichresults in warming. Further, it can be seen that in the presentinvention I have provided a method and agents which when applied to baldscalp causes hair growth through utilization of one of the body's ownmechanisms. This effect is achieved by providing the biochemicalsubstrate at the local site from which the controlling substance, nitricoxide is produced. Nitric oxide causes increases in local blood flowwhich enables the growth of hair. Still further it can be seen that inthe present invention I have provided a method and agents which whenapplied to leg ulcers cause healing through use of the body's ownmechanisms. Yet still further, it can be seen that in the presentinvention I have provided a method and agents which when applied to aperson with impotence causes overcoming of impotence by use of thebody's own mechanisms. This effect is achieved by providing thebiochemical substrate at the local site from which the controllingsubstance, nitric oxide is produced. Nitric oxide causes increases inlocal blood flow allowing the body's own healing cells and substances toreach the ulcer site.

[0029] Although the description above contains many specificities, theseshould not be construed as limiting the scope of the invention but asmerely providing illustrations of some of the presently preferredembodiments of this invention. Various other embodiments andramifications are possible within this scope.

[0030] Thus the scope of the invention should be determined by theappended claims and their legal equivalents, rather than by the examplesgiven.

What is claimed is:
 1. A method for delivering a nitric oxide precursorto an area of the body for the purpose of increasing local blood flow.2. The method of claim 1 where the delivery vehicle is orallyadministered forms of L-arginine such as capsules, tablets, liquid orother oral form in dosage sufficient to produce the desired effect. 3.The method of claim 1 where the delivery vehicles are orallyadministered L-arginine used in conjunction with a penetrating cream, aliquid, a lotion, an ointment or other topical preparation containingL-arginine, salt or salts of L-arginine, a complex of L-arginine or aderivative of L-arginine in an effective dose.
 4. The method of claim 1where the delivery vehicle are orally administered L-arginine used inconjunction with a penetrating cream, a liquid, a lotion, an ointment orother topical preparation containing L-arginine, salt or salts ofL-arginine, a complex of L-arginine or a derivative of L-arginine in aneffective dose in addition to other ionic salts such as to create anionic strength environment high enough to provide an extra force tocause tissue absorption of the L-arginine species.
 5. The method ofclaim 1 where the delivery vehicle is orally administered L-arginineused in conjunction with a penetrating cream of hydrophobic naturecontaining little or no water, but oils, waxes and other hydrophobicsubstances, containing L-arginine, salt or salts of L-arginine, acomplex of L-arginine or a derivative of L-arginine in an effectivedose.
 6. The method of claim 1 where the delivery vehicle is orallyadministered L-arginine used in conjunction with a penetrating cream, aliquid, a lotion, an ointment or other topical preparation containingliposomes or liposome like structures which contain within themL-arginine, salt or salts of L-arginine, a complex of L-arginine or aderivative of L-arginine in an effective dose.
 7. The method of claim 1where the delivery vehicle is orally administered L-arginine used inconjunction with a penetrating cream, a liquid, a lotion, an ointment orother topical preparation containing liposomes in which are encapsulatedL-arginine, salt or salts of L-arginine in an effective dose in additionto other ionic salts such as to create an ionic strength environmenthigh enough to provide extra force to cause absorption of the L-argininespecies.
 8. The method of claim 1 where the delivery vehicle is orallyadministered L-arginine used in conjunction with a trans-dermal patch orits equivalent where the patch contains L-arginine, a salt or salts ofL-arginine, a complex of L-arginine or a derivative of L-arginine in aneffective dose.
 9. The method of claim 1 where the delivery vehicle isorally administered L-arginine used in conjunction with a trans-dermalpatch or its equivalent where the patch contains L-arginine, a salt orsalts of L-arginine, a complex of L-arginine or a derivative ofL-arginine in an effective dose in addition to other ionic salts such asto create an ionic strength environment high enough to provide extraforce to cause tissue absorption of the L-arginine species.
 10. Themethod of claim 1 where the delivery vehicle is orally administeredL-arginine (0.5-30 g/day) used in conjunction with a cream containingwater, aloe vera, mineral oil, glycerol stearate, squalene, wheat germoil, cetyl alcohol, propylene glycol stearate, polysorbate 60, propyleneglycol, vitamin E, hyaluronic acid/collagen, vitamin A, vitamin D,sorbitan stearate, triethanolamine, imidazolidinyl urea, methylparaben,propylparaben, bha, L-arginine hydrochloride (0.25% to 25%) and sodiumchloride (0.25% to 25%).
 11. The method of claim 1 where the deliveryvehicle is orally administered L-arginine (0.5-30 g/day) used inconjunction with a cream containing water, aloe vera, mineral oil,glycerol stearate, squalene, wheat germ oil, cetyl alcohol, propyleneglycol stearate, polysorbate 60, propylene glycol, vitamin E, hyaluronicacid/collagen, vitamin A, vitamin D, sorbitan stearate, triethanolamine,imidazolidinyl urea, methylparaben, propylparaben, bha, L-arginineglutamate (0.25% to 25%) and sodium chloride (0.25%-25%).
 12. The methodof claim 1 where the delivery vehicle is orally administered L-arginine(0.5-30 g/day) in conjunction with a cream containing water, aloe vera,mineral oil, glycerol stearate, squalene, wheat germ oil, cetyl alcohol,propylene glycol stearate, polysorbate 60, propylene glycol, vitamin E,hyaluronic acid/collagen, vitamin A, vitamin D, sorbitan stearate,triethanolamine, imidazolidinyl urea, methylparaben, propylparaben, bha,L-arginine (0.25% to 25%) and choline chloride (0.25% to 25%).
 13. Amethod for warming cool or cold tissue by providing, through means of adelivery vehicle, to the cold or cool tissue an effective dose of aprecursor to the endothelial relaxing factor, nitric oxide.
 14. Themethod of claim 13 where the delivery vehicle is orally administeredL-arginine contained in capsules, tablets, liquid or other oral form indosage sufficient to cause the desired effect.
 15. The method of claim13 where the delivery vehicle is orally administered L-arginine used inconjunction with a penetrating cream, a liquid, a lotion, and ointmentor other topical preparation containing L-arginine, salt or salts ofL-arginine, a complex of L-arginine or a derivative of L-arginine in aneffective dose.
 16. The method of claim 13 where the delivery vehicle isorally administered L-arginine used in conjunction with a penetratingcream, a liquid, a lotion, an ointment or other topical preparationcontaining L-arginine, salt or salts of L-arginine, a complex ofL-arginine or a derivative of L-arginine in an effective dose inaddition to other ionic salts such as to create an ionic strengthenvironment high enough to provide an extra force to cause tissueabsorption of the L-arginine species.
 17. The method of claim 13 wherethe delivery vehicle is orally administered L-arginine used inconjunction with a penetrating cream of hydrophobic nature containingoils, waxes and other hydrophobic materials and little water sufficientto aid in the absorption of the nitric oxide precursor L-arginine, saltor salts of L-arginine, a complex of L-arginine or a derivative ofL-arginine in an effective dose.
 18. The method of claim 13 where thedelivery vehicle is orally administered L-arginine used in conjunctionwith a penetrating cream, a liquid, a lotion, an ointment or othertopical preparation containing liposomes in which are encapsulatedL-arginine, salt or salts of L-arginine, a complex of L-arginine or aderivative of L-arginine in an effective dose.
 19. The method of claim13 where the delivery vehicle is orally administered L-arginine inconjunction with a penetrating cream, a liquid, a lotion, an ointment orother topical preparation containing liposomes in which are encapsulatedL-arginine, salt or salts of L-arginine, a complex of L-arginine or aderivative of L-arginine in an effective dose in addition to other ionicsalts such as to create an ionic strength environment high enough toprovide extra force to cause absorption of the L-arginine species. 20.The method of claim 13 where the delivery vehicle is orally administeredL-arginine administered in conjunction with a trans-dermal patch or itsequivalent where the patch contains L-arginine, a salt or salts ofL-arginine, a complex of L-arginine or a derivative of L-arginine in aneffective dose.
 21. The method of claim 13 where the delivery vehicle isorally administered L-arginine administered in conjunction with atrans-dermal patch or its equivalent where the patch containsL-arginine, a salt or salts of L-arginine, a complex of L-arginine or aderivative of L-arginine in an effective dose in addition to other ionicsalts such as to create an ionic strength environment high enough toprovide an extra force to cause tissue absorption of the L-argininespecies.
 22. The method of claim 13 where the delivery vehicle is orallyadministered L-arginine (0.5-30 g/day) administered in conjunction witha cream containing water, aloe vera, mineral oil, glycerol stearate,squalene, wheat germ oil, cetyl alcohol, propylene glycol stearate,polysorbate 60, propylene glycol, vitamin E, hyaluronic acid/collagen,vitamin A, vitamin D, sorbitan stearate, triethanolamine, imidazolidinylurea, methylparaben, propylparaben, bha, L-arginine hydrochloride (0.25%to 25%) and sodium chloride (0.25% to 25%).
 23. The method of claim 13where the delivery vehicle is orally administered L-arginine (0.5-30g/day) administered in conjunction with a cream containing water, aloevera, mineral oil, glycerol stearate, squalene, wheat germ oil, cetylalcohol, propylene glycol stearate, polysorbate 60, propylene glycol,vitamin E, hyaluronic acid/collagen, vitamin A, vitamin D, sorbitanstearate, triethanolamine, imidazolidinyl urea, methylparaben,propylparaben, bha, L-arginine glutamate (0.25% to 25%) and sodiumchloride (0.25%-25%).
 24. The method of claim 13 where the deliveryvehicle is orally administered L-arginine (0.5-30 g/day) administered inconjunction with a cream containing water, aloe vera, mineral oil,glycerol stearate, squalene, wheat germ oil, cetyl alcohol, propyleneglycol stearate, polysorbate 60, propylene glycol, vitamin E, hyaluronicacid/collagen, vitamin A, vitamin D, sorbitan stearate, triethanolamine,imidazolidinyl urea, methylparaben, propylparaben, bha, L-arginine(0.25% to 25%) and choline chloride (0.25% to 25%).
 25. A method forpromoting hair growth on bald scalp, through means of a deliveryvehicle, to the bald scalp an effective dose of a precursor to theendothelial relaxing factor, nitric oxide.
 26. The method of claim 25where the delivery vehicle is orally administered L-arginine containedin capsules, tablets, liquid or other oral form at a dosage sufficientto obtain the desired effect.
 27. The method of claim 25 where thedelivery vehicle is orally administered L-arginine administered inconjunction with a penetrating cream, a liquid, a lotion, and ointmentor other topical preparation containing L-arginine, salt or salts ofL-arginine, a complex of L-arginine or a derivative of L-arginine in aneffective dose.
 28. The method of claim 25 where the delivery vehicle isorally administered L-arginine use in conjunction with a penetratingcream, a liquid, a lotion, an ointment or other topical preparationcontaining L-arginine, salt or salts of L-arginine, a complex ofL-arginine or a derivative of L-arginine in an effective dose inaddition to other ionic salts such as to create an ionic strengthenvironment high enough to provide an extra force to cause tissueabsorption of the L-arginine species.
 29. The method of claim 25 wherethe delivery vehicle is orally administered L-arginine used inconjunction with a penetrating cream of hydrophobic nature containingoils, waxes and other hydrophobic materials and little water sufficientto aid in the absorption of the nitric oxide precursor L-arginine, saltor salts of L-arginine, a complex of L-arginine or a derivative ofL-arginine in an effective dose.
 30. The method of claim 25 where thedelivery vehicle is orally administered L-arginine used in conjunctionwith a penetrating cream, a liquid, a lotion, an ointment or othertopical preparation containing liposomes in which are encapsulatedL-arginine, salt or salts of L-arginine, a complex of L-arginine or aderivative of L-arginine in an effective dose.
 31. The method of claim25 where the delivery vehicle is orally administered L-arginine used inconjunction with a penetrating cream, a liquid, a lotion, an ointment orother topical preparation containing liposomes in which are encapsulatedL-arginine, salt or salts of L-arginine, a complex of L-arginine or aderivative of L-arginine in an effective dose in addition to other ionicsalts such as to create an ionic strength environment high enough toprovide extra force to cause absorption of the L-arginine species. 32.The method of claim 25 where the delivery vehicle is orally administeredL-arginine used in conjunction with a trans-dermal patch or itsequivalent where the patch contains L-arginine, a salt or salts ofL-arginine, a complex of L-arginine or a derivative of L-arginine in aneffective dose.
 33. The method of claim 25 where the delivery vehicle isorally administered L-arginine used in conjunction with a trans-dermalpatch or its equivalent where the patch contains L-arginine, a salt orsalts of L-arginine, a complex of L-arginine or a derivative ofL-arginine in an effective dose in addition to other ionic salts such asto create an ionic strength environment high enough to provide an extraforce to cause tissue absorption of the L-arginine species.
 34. Themethod of claim 25 where the delivery vehicle is orally administeredL-arginine (0.5-30 g/day) used in conjunction with a cream containingwater, aloe vera, mineral oil, glycerol stearate, squalene, wheat germoil, cetyl alcohol, propylene glycol stearate, polysorbate 60, propyleneglycol, vitamin E, hyaluronic acid/collagen, vitamin A, vitamin D,sorbitan stearate, triethanolamine, imidazolidinyl urea, methylparaben,propylparaben, bha, L-arginine hydrochloride (0.25% to 25%) and sodiumchloride (0.25% to 25%).
 35. The method of claim 25 where the deliveryvehicle is orally administered L-arginine (0.5-30 g/day) used inconjunction with a cream containing water, aloe vera, mineral oil,glycerol stearate, squalene, wheat germ oil, cetyl alcohol, propyleneglycol stearate, polysorbate 60, propylene glycol, vitamin E, hyaluronicacid/collagen, vitamin A, vitamin D, sorbitan stearate, triethanolamine,imidazolidinyl urea, methylparaben, propylparaben, bha, L-arginineglutamate (0.25% to 25%) and sodium chloride (0.25%-25%).
 36. The methodof claim 25 where the delivery vehicle is orally administered L-arginine(0.5-30 g/day) used in conjunction with a cream containing water, aloevera, mineral oil, glycerol stearate, squalene, wheat germ oil, cetylalcohol, propylene glycol stearate, polysorbate 60, propylene glycol,vitamin E, hyaluronic acid/collagen, vitamin A, vitamin D, sorbitanstearate, triethanolamine, imidazolidinyl urea, methylparaben,propylparaben, bha, L-arginine (0.25% to 25%) and choline chloride(0.25% to 25%).
 37. A method for promoting healing of superficial ulcerssuch as leg ulcers secondary to diabetes or other causes, through meansof a delivery vehicle, to the ulcer and the area surrounding it aneffective dose of a precursor to the endothelial relaxing factor, nitricoxide.
 38. The method of claim 37 where the delivery vehicle is orallyadministered L-arginine in capsules, tablets, liquid or other oral formsin a dosage sufficient to produce the desired effect.
 39. The method ofclaim 37 where the delivery vehicle is orally administered L-arginineused in conjunction with a penetrating cream, a liquid, a lotion, andointment or other topical preparation containing L-arginine, salt orsalts of L-arginine, a complex of L-arginine or a derivative ofL-arginine in an effective dose.
 40. The method of claim 37 where thedelivery vehicle is orally administered L-arginine used in conjunctionwith a penetrating cream, a liquid, a lotion, an ointment or othertopical preparation containing L-arginine, salt or salts of L-arginine,a complex of L-arginine or a derivative of L-arginine in an effectivedose in addition to other ionic salts such as to create an ionicstrength environment high enough to provide an extra force to causetissue absorption of the L-arginine species.
 41. The method of claim 37where the delivery vehicle is orally administered L-arginineadministered in conjunction with a penetrating cream of hydrophobicnature containing oils, waxes and other hydrophobic materials and littlewater sufficient to aid in the absorption of the nitric oxide precursorL-arginine, salt or salts of L-arginine, a complex of L-arginine or aderivative of L-arginine in an effective dose.
 42. The method of claim37 where the delivery vehicle is orally administered L-arginine used inconjunction with a penetrating cream, a liquid, a lotion, an ointment orother topical preparation containing liposomes in which are encapsulatedL-arginine, salt or salts of L-arginine, a complex of L-arginine or aderivative of L-arginine in an effective dose.
 43. The method of claim37 where the delivery vehicle is orally administered L-arginine used inconjunction with a penetrating cream, a liquid, a lotion, an ointment orother topical preparation containing liposomes in which are encapsulatedL-arginine, salt or salts of L-arginine, a complex of L-arginine or aderivative of L-arginine in an effective dose in addition to other ionicsalts such as to create an ionic strength environment high enough toprovide extra force to cause absorption of the L-arginine species. 44.The method of claim 37 where the delivery vehicle is orally administeredL-arginine used in conjunction with a trans-dermal patch or itsequivalent where the patch contains L-arginine, a salt or salts ofL-arginine, a complex of L-arginine or a derivative of L-arginine in aneffective dose.
 45. The method of claim 37 where the delivery vehicle isorally administered L-arginine used in conjunction with a trans-dermalpatch or its equivalent where the patch contains L-arginine, a salt orsalts of L-arginine, a complex of L-arginine or a derivative ofL-arginine in an effective dose in addition to other ionic salts such asto create an ionic strength environment high enough to provide an extraforce to cause tissue absorption of the L-arginine species.
 46. Themethod of claim 37 where the delivery vehicle is orally administeredL-arginine (0.5-30 g/day) used in conjunction with a cream containingwater, aloe vera, mineral oil, glycerol stearate, squalene, wheat germoil, cetyl alcohol, propylene glycol stearate, polysorbate 60, propyleneglycol, vitamin E, hyaluronic acid/collagen, vitamin A, vitamin D,sorbitan stearate, triethanolamine, imidazolidinyl urea, methylparaben,propylparaben, bha, L-arginine hydrochloride (0.25% to 25%) and sodiumchloride (0.25% to 25%).
 47. The method of claim 37 where the deliveryvehicle is orally administered L-arginine (0.5-30 g/day) used inconjunction with a cream containing water, aloe vera, mineral oil,glycerol stearate, squalene, wheat germ oil, cetyl alcohol, propyleneglycol stearate, polysorbate 60, propylene glycol, vitamin E, hyaluronicacid/collagen, vitamin A, vitamin D, sorbitan stearate, triethanolamine,imidazolidinyl urea, methylparaben, propylparaben, bha, L-arginineglutamate (0.25% to 25%) and sodium chloride (0.25%-25%).
 48. The methodof claim 37 where the delivery vehicle is orally administered L-arginine(0.5-30 g/day) used in conjunction with a cream containing water, aloevera, mineral oil, glycerol stearate, squalene, wheat germ oil, cetylalcohol, propylene glycol stearate, polysorbate 60, propylene glycol,vitamin E, hyaluronic acid/collagen, vitamin A, vitamin D, sorbitanstearate, triethanolamine, imidazolidinyl urea, methylparaben,propylparaben, bha, L-arginine (0.25% to 25%) and choline chloride(0.25% to 25%).
 49. A method for overcoming impotence by delivering tothe penis an effective dose of a precursor to the endothelial relaxingfactor, nitric oxide.
 50. The method of claim 49 where the deliveryvehicle is orally administered L-arginine in capsules, tablets, liquidor other oral forms in a dosage sufficient to produce the desiredeffect.
 51. The method of claim 49 where the delivery vehicle is orallyadministered L-arginine used in conjunction with a penetrating cream, aliquid, a lotion, and ointment or other topical preparation containingL-arginine, salt or salts of L-arginine, a complex of L-arginine or aderivative of L-arginine in an effective dose.
 52. The method of claim49 where the delivery vehicle is orally administered L-arginine used inconjunction with a penetrating cream, a liquid, a lotion, an ointment orother topical preparation containing L-arginine, salt or salts ofL-arginine, a complex of L-arginine or a derivative of L-arginine in aneffective dose in addition to other ionic salts such as to create anionic strength environment high enough to provide an extra force tocause tissue absorption of the L-arginine species.
 53. The method ofclaim 49 where the delivery vehicle is orally administered L-arginineadministered in conjunction with a penetrating cream of hydrophobicnature containing oils, waxes and other hydrophobic materials and littlewater sufficient to aid in the absorption of the nitric oxide precursorL-arginine, salt or salts of L-arginine, a complex of L-arginine or aderivative of L-arginine in an effective dose.
 54. The method of claim49 where the delivery vehicle is orally administered L-arginine used inconjunction with a penetrating cream, a liquid, a lotion, an ointment orother topical preparation containing liposomes in which are encapsulatedL-arginine, salt or salts of L-arginine, a complex of L-arginine or aderivative of L-arginine in an effective dose.
 55. The method of claim49 where the delivery vehicle is orally administered L-arginine used inconjunction with a penetrating cream, a liquid, a lotion, an ointment orother topical preparation containing liposomes in which are encapsulatedL-arginine, salt or salts of L-arginine, a complex of L-arginine or aderivative of L-arginine in an effective dose in addition to other ionicsalts such as to create an ionic strength environment high enough toprovide extra force to cause absorption of the L-arginine species. 56.The method of claim 49 where the delivery vehicle is orally administeredL-arginine used in conjunction with a trans-dermal patch or itsequivalent where the patch contains L-arginine, a salt or salts ofL-arginine, a complex of L-arginine or a derivative of L-arginine in aneffective dose.
 57. The method of claim 49 where the delivery vehicle isorally administered L-arginine used in conjunction with a trans-dermalpatch or its equivalent where the patch contains L-arginine, a salt orsalts of L-arginine, a complex of L-arginine or a derivative ofL-arginine in an effective dose in addition to other ionic salts such asto create an ionic strength environment high enough to provide an extraforce to cause tissue absorption of the L-arginine species.
 58. Themethod of claim 49 where the delivery vehicle is orally administeredL-arginine (0.5-30 g/day) used in conjunction with a cream containingwater, aloe vera, mineral oil, glycerol stearate, squalene, wheat germoil, cetyl alcohol, propylene glycol stearate, polysorbate 60, propyleneglycol, vitamin E, hyaluronic acid/collagen, vitamin A, vitamin D,sorbitan stearate, triethanolamine, imidazolidinyl urea, methylparaben,propylparaben, bha, L-arginine hydrochloride (0.25% to 25%) and sodiumchloride (0.25% to 25%).
 59. The method of claim 49 where the deliveryvehicle is orally administered L-arginine (0.5-30 g/day) used inconjunction with a cream containing water, aloe vera, mineral oil,glycerol stearate, squalene, wheat germ oil, cetyl alcohol, propyleneglycol stearate, polysorbate 60, propylene glycol, vitamin E, hyaluronicacid/collagen, vitamin A, vitamin D, sorbitan stearate, triethanolamine,imidazolidinyl urea, methylparaben, propylparaben, bha, L-arginineglutamate (0.25% to 25%) and sodium chloride (0.25%-25%).
 60. The methodof claim 49 where the delivery vehicle is orally administered L-arginine(0.5-30 g/day) used in conjunction with a cream containing water, aloevera, mineral oil, glycerol stearate, squalene, wheat germ oil, cetylalcohol, propylene glycol stearate, polysorbate 60, propylene glycol,vitamin E, hyaluronic acid/collagen, vitamin A, vitamin D, sorbitanstearate, triethanolamine, imidazolidinyl urea, methylparaben,propylparaben, bha, L-arginine (0.25% to 25%) and choline chloride(0.25% to 25%).